Global networks form to take on the problem of drug-induced liver injury (DILI)

Posted on May 20th, 2020 by Xuanyan Xu in Pharma R&D

Drug-induced liver injury (DILI), which is one of the top causes of liver failure in the United States [1], is an adverse reaction that can be caused by a significant number of medications. DILI can be fatal and is not only a major concern post-market, but also during drug development as it is the top safety-related reason for late-stage clinical trial failure.

The international
pharmaceutical research community has been working together to help take on the
problem of drug-induced liver injury by establishing networks, consortia and
partnerships designed to understand more about DILI.

For example, the Drug-Induced Liver Injury Network (DILIN) was formed by the National Institute of Diabetes and Digestive and Kidney Diseases with the aim of identifying and analyzing severe liver injury cases that were caused by both prescription and over-the-counter drugs, as well as alternative and herbal medicines. The efforts of DILIN’s experts is to determine the degree of impact that each medication has on liver injury, which would allow pharmaceutical companies to improve their DILI risk assessment, especially in patients taking multiple drugs.

Currently DILIN is
working on two noteworthy studies to:

1) establish a
registry of people who have experienced liver injury in the past 10 years using
drugs or herbal / dietary supplements, and

2) establish a registry of people who have experienced liver injury in the past
six months after using certain drugs or alternative products.

The Spanish DILI Registry began in 1994, establishing a network of clinician-pharmacists and hepatologists to identify cases of liver damage caused by drugs. Since then, the organization has sought to share its methodologies and expand its international reach further by creating the Spanish-Latin American DILI Network (SLATINDILI), which includes Argentina, Brazil, Chile, Ecuador, Mexico, Paraguay, Peru and Venezuela.

In 2014, they went on to start a European network called the Pro-Euro DILI Registry, which has since been working on enabling the development and implementation of novel safety biomarkers in clinical trials and diagnosis of disease.

China, too, is collecting important data and creating a powerful DILI resource with Hepatox.org, a clinical database, application and information platform focused on DILI. Researchers can look there to find the latest information and resources relevant to DILI, medical liver injury cases, an online DILI evaluation tool, research registration, a management system for clinical trials, and more.

The IQ-DILI Initiative, affiliated with the International Consortium for Innovation and Quality in Pharmaceutical Development, is another organization taking on DILI. Their mission is to define best practices for the detection, monitoring, management and prevention of DILI in clinical trials and pharmacovigilance programs.

In December 2019, IQ-DILI published the paper “Consensus guidelines: best practices for detection, assessment and management of suspected acute drug-induced liver injury occurring during clinical trials in adults with chronic cholestatic liver disease.” IQ-DILI reported in February 2020 that the paper was one of the most downloaded papers published in Alimentary Pharmacology & Therapeutics, demonstrating how critical DILI risk assessment is to the industry.

As we discussed in an earlier post, even Elsevier has gotten involved, partnering with the FDA to work on developing a model to predict DILI. Similarly, the DILI-sim Initiative, a partnership that includes the Hamner Institutes for Health Sciences, has the goal of developing a computational model that can predict if a new drug candidate could cause drug-induced liver injury.

With so much of the
global pharma community banding together, we hope that it won’t be long until
DILI is better understood by researchers, and eventually easier to avoid or
prevent in drug development and beyond.

REFERENCES

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3467427

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